title: Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination.
abstract: The Mpk1 MAPK of the yeast cell wall integrity pathway uses a noncatalytic mechanism to activate transcription of stress-induced genes by recruitment of initiation factors to target promoters. We show here that Mpk1 additionally serves a function in transcription elongation that is also independent of its catalytic activity. This function is mediated by an interaction between Mpk1 and the Paf1 subunit of the Paf1C elongation complex. A mutation in Paf1 that blocks this interaction causes a specific defect in transcription elongation of an Mpk1-induced gene, which results from Sen1-dependent premature termination through a Nab3-binding site within the promoter-proximal region of the gene. Our findings reveal a regulatory mechanism in which Mpk1 overcomes transcriptional attenuation by blocking recruitment of the Sen1-Nrd1-Nab3 termination complex to the elongating polymerase. Finally, we demonstrate that this mechanism is conserved in an interaction between the human ERK5 MAPK and human Paf1.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Kim
authors.forename: David E
authors.initials: DE
authors.lastname: Levin
mesh_terms: D004265:DNA Helicases / Q000378:metabolism*; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; C501972:PAF1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005964:Glucosyltransferases; C095724:GSC2 protein, S cerevisiae; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; C542347:SEN1 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases